产品描述:
PF-06650833 is an inhibitor of IL-1 receptor-associated kinase 4 (IRAK4; IC50 = 0.2 nM).{46434} It is selective for IRAK4 over a panel of 268 kinases at 200 nM but also inhibits IRAK1, MAP kinase-interacting serine/threonine protein kinase 2 (MNK2), leucine-rich repeat kinase 2 (LRRK2), CDC-like kinase 4 (Clk4), and casein kinase 1γ1 (CK1γ1) by greater than 70% at 200 nM. PF-06650833 (100 nM) reduces secretion of DNA from primary human neutrophils stimulated by the toll-like receptor 7 (TLR7) agonist R-837 (imiquimod; Item No. 14956) and decreases IFN regulatory factor 5 (IRF5) nuclear translocation induced by the synthetic TLR7/8 ligand R-848 (Item No. 14806) in primary human peripheral blood mononuclear cells (PMBCs).{66714} It decreases paw volume in a rat model of collagen-induced arthritis when administered at a dose of 100 mg/kg once per day.{46434} Dietary administration of PF-06650833 reduces serum levels of the autoantibodies anti-dsDNA, anti-SSA, and anti-RNP and decreases kidney glomerular tuft area in a mouse model of systemic lupus erythematosus (SLE) induced by the isoprenoid alkane pristane.{66714}